Evidence map›Paper›PMID 29470517›Full record

ArticlePLoS pathogens2018

Two essential Thioredoxins mediate apicoplast biogenesis, protein import, and gene expression in Toxoplasma gondii.

Marco Biddau, Anne Bouchut, Jack Major, Tracy Saveria, Julie Tottey, Ojore Oka, Marcel van-Lith, Katherine Elizabeth Jennings, Jana Ovciarikova, Amy DeRocher and 4 more

Open access · goldAbstract readComparative Study
In one paragraph

Article in PLoS pathogens, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.

0numbers the graph read from it
0cells of the map it votes in
28citing papers in PubMed
2.6field-weighted citation impact, top 9% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

28 citing papers in PubMed, 62 citations in OpenAlex.

  1. Article
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  5. Article
  6. The Major Facilitator Superfamily Transporter HAP12 Is Critical inInternational journal of molecular sciences · 2025
    Article
  7. Reference Gene Selection for RT-qPCR Normalization inInternational journal of molecular sciences · 2024
    Article
  8. Article
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  10. Article
  11. RNA-Seq of Phenotypically DistinctPathogens (Basel, Switzerland) · 2023
    Article
  12. Article
  13. Article
  14. Article
  15. Identification and Function of Apicoplast Glutaredoxins inInternational journal of molecular sciences · 2021
    Article
  16. Article
  17. Article
  18. Article
  19. Article
  20. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

14 authors at 5 institutions in 2 countries.

Marco BiddauWellcome Centre for Molecular Parasitology, University of Glasgow, 120 University Place Glasgow, United Kingdom.ORCID 0000-0002-9992-0418
Anne BouchutCenter for Infectious Disease Research, Seattle, WA, United States of America.
Jack MajorWellcome Centre for Molecular Parasitology, University of Glasgow, 120 University Place Glasgow, United Kingdom.
Tracy SaveriaCenter for Infectious Disease Research, Seattle, WA, United States of America.
Julie TotteyWellcome Centre for Molecular Parasitology, University of Glasgow, 120 University Place Glasgow, United Kingdom.ORCID 0000-0001-6500-1117
Ojore OkaInstitute of Molecular Cell and Systems Biology, Wolfson Link Building, University of Glasgow, Glasgow, United Kingdom.ORCID 0000-0003-3482-115X
Marcel van-LithInstitute of Molecular Cell and Systems Biology, Wolfson Link Building, University of Glasgow, Glasgow, United Kingdom.
Katherine Elizabeth JenningsCenter for Tropical & Emerging Global Diseases, University of Georgia, Brooks Dr. Athens, GA, United States of America.ORCID 0000-0003-2881-7306
Jana OvciarikovaWellcome Centre for Molecular Parasitology, University of Glasgow, 120 University Place Glasgow, United Kingdom.
Amy DeRocherCenter for Infectious Disease Research, Seattle, WA, United States of America.ORCID 0000-0003-1205-7920
Boris StriepenCenter for Tropical & Emerging Global Diseases, University of Georgia, Brooks Dr. Athens, GA, United States of America.
Ross Frederick WallerDepartment of Biochemistry, University of Cambridge, Cambridge, United Kingdom.ORCID 0000-0001-6961-9344
Marilyn ParsonsCenter for Infectious Disease Research, Seattle, WA, United States of America.ORCID 0000-0003-3994-8096
Lilach SheinerWellcome Centre for Molecular Parasitology, University of Glasgow, 120 University Place Glasgow, United Kingdom.ORCID 0000-0001-5909-2307
Wellcome Centre for Molecular Parasitology · GBCenter for Infectious Disease Research · USInstitute of Structural and Molecular Biology · GBUniversity of Georgia · USUniversity of Cambridge · GB

Funding

The Plastid of Toxoplasma gondiiR01AI050506 · NIAID · SEATTLE BIOMEDICAL RESEARCH INSTITUTE · PI PARSONS, MARILYN · 2002 to 2012
$4.7M
Unique functions of the mitochondrial tRNA import machinety in T. gondiiK99AI103032 · NIAID · UNIVERSITY OF GEORGIA · PI SHEINER, LILACH · 2013 to 2013
$90k
Medical Research Council MC_PC_16073Medical Research Council MR/M011690/1NIAID NIH HHS K99 AI103032NIAID NIH HHS R01 AI050506NIH HHS K99 AI103032NIH HHS R01 AI08441Wellcome Trust
6 · The paper itself

Abstract

Apicomplexan parasites are global killers, being the causative agents of diseases like toxoplasmosis and malaria. These parasites are known to be hypersensitive to redox imbalance, yet little is understood about the cellular roles of their various redox regulators. The apicoplast, an essential plastid organelle, is a verified apicomplexan drug target. Nuclear-encoded apicoplast proteins traffic through the ER and multiple apicoplast sub-compartments to their place of function. We propose that thioredoxins contribute to the control of protein trafficking and of protein function within these apicoplast compartments. We studied the role of two Toxoplasma gondii apicoplast thioredoxins (TgATrx), both essential for parasite survival. By describing the cellular phenotypes of the conditional depletion of either of these redox regulated enzymes we show that each of them contributes to a different apicoplast biogenesis pathway. We provide evidence for TgATrx1's involvement in ER to apicoplast trafficking and TgATrx2 in the control of apicoplast gene expression components. Substrate pull-down further recognizes gene expression factors that interact with TgATrx2. We use genetic complementation to demonstrate that the function of both TgATrxs is dependent on their disulphide exchange activity. Finally, TgATrx2 is divergent from human thioredoxins. We demonstrate its activity in vitro thus providing scope for drug screening. Our study represents the first functional characterization of thioredoxins in Toxoplasma, highlights the importance of redox regulation of apicoplast functions and provides new tools to study redox biology in these parasites.

Indexed as

Gene Expression Regulation, DevelopmentalOrganelle BiogenesisAmino Acid SequenceApicoplastsBiomarkersConserved SequenceEvolution, MolecularGene Knockdown TechniquesLuminescent ProteinsMicroscopy, FluorescenceMutationPhylogenyProtein IsoformsProtein MultimerizationProtein TransportRecombinant Fusion ProteinsBiomarkersLuminescent ProteinsProtein IsoformsRecombinant Fusion ProteinsThioredoxins

Identifiers

PMID29470517
PMCPMC5823475
OpenAlexW2787918313

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.